1. Field of the Invention
The invention relates to polymeric articles capable of releasing drugs at therapeutic levels over extended periods of time, and to methods for producing the extended release articles.
2. Description of the Related Art
An ideal drug delivery system has been suggested to be one which provides the drug only when and where it is needed, and in the minimum dosage required to elicit the desired therapeutic effects. Extended release technology permits delivery to a patient of drug concentrations at therapeutic levels for extended periods without repeated dosage and consequent cycling concentrations.
A great many specific systems for controlled release of drugs from polymers have previously been described. These systems may be broadly classified as follows:                Bioerodible systems. e.g., WO 2009/129439 A2        Drug-polymer chemical conjugates        Membrane-reservoir systems        Osmotic pumping        Osmotic rupturing. e.g., U.S. Pat. No. 5,302,397        Porous polymers        Polymer erosion        Polymer swelling        Diffusion through a matrix        
This latter approach of diffusion through a matrix has been extensively employed for example in U.S. Pat. Nos. 4,863,444; 6,361,526 B1; 6,641,831 B1; 6,723,333 B1; United States Patent Applications 2009/0076480 A1; 2009/0171465; and in publications such as:
Sprockel et al, “A Melt Extrusion Process For Manufacturing Matrix Drug Delivery Systems”, Int. J. Pharmaceutics, 155, 191-199 (1997)
Schierholz et al., “Controlled Release of Antibiotics From Biomedical Polyurethanes: Morphological and Structural Features”. Biomaterials, 18, No. 12, 839-844 (1997)
P. I Lee and W. R. Good, Eds., “Overview of Controlled-Release Drug Delivery” in “Controlled Release Technology”, ACS Symposium Series 348, American Chemical Society, Washington, D., 1987
Drug delivery by diffusion through a matrix has been described and criticized as follows:                “Historically, the most popular diffusion-controlled delivery system has been the matrix system, such as tablet and granules, where the drug is uniformly dissolved or dispersed, because of its low cost and ease of fabrication. However, the inherent drawback of the matrix system is its first-order release behavior with continuously diminishing release rate.” (emphasized in original)        P. I Lee and W. R. Good, Eds., “Controlled Release Technology”, American Chemical Society, Washington, D., P. 5, 1987        
The articles of the invention are solid, non-porous composites prepared by uniformly dispersing a bioactive agent in a non-biodegradable thermoplastic polymer melt, then cooling to a non-porous solid state. The composite may be formed into useful articles by standard methods of plastics processing such as extrusion, compression, or injection molding. The drug is released by diffusion through the polymer matrix. The inventive articles have the merits of low cost and ease of fabrication combined with extended drug release and essentially constant drug release rate after an initial induction period. Examples of the inventive articles containing antibiotics have long term antibacterial effect without cytotoxicity to fibroblasts. This surprising combination of properties satisfies long standing, but unmet needs.